A Human Islet Cell Culture System for High-Throughput Screening

A small-molecule inducer of beta-cell proliferation in human islets represents a potential regeneration strategy for treating type 1 diabetes. However, the lack of suitable human beta cell lines makes such a discovery a challenge. Here, we adapted an islet cell culture system to high-throughput screening to identify such small molecules. We prepared microtiter plates containing extracellular matrix from a human bladder carcinoma cell line. Dissociated human islets were seeded onto these plates, cultured for up to 7 days, and assessed for proliferation by simultaneous Ki67 and C-peptide immunofluorescence. Importantly, this environment preserved beta-cell physiological function, as measured by glucose-stimulated insulin secretion. Adenoviral overexpression of cdk-6 and cyclin D1, known inducers of human beta cell proliferation, was used as a positive control in our assay. This induction was inhibited by cotreatment with rapamycin, an immunosuppressant often used in islet transplantation. We then performed a pilot screen of 1280 compounds, observing some phenotypic effects on cells. This high-throughput human islet cell culture method can be used to assess various aspects of beta-cell biology on a relatively large number of compounds.

Effect of islet cell culture xenotransplantation on alloxan diabetes course in rats fed diets with different protein content

The authors present data- on the protective effect of newborn rabbits pancreatic islet cell culture xenotransplantation of Langerhans islets P-cells of rats with alloxan diabetes. This effect was the most marked in rats fed diets with normal or increased protein content. The authors discuss a possible stimulating effect of rabbit islet cell culture xenooransplantation on regeneration processes in recipient rat pancreatic islets. This effect was better pronounced in rats kept on rations with increased protein content. Further experiments will help more accuretaly define the indications for therapy of insulindependent diabetes mellitus by xenokansplantations of islet cell cultures.